The Pharmacovigilance Risk

Assessment Committee

GPvP Symposium, 14 March 2014

Dr Julie Williams, PRAC Delegate

Scope of presentation

• Establishing PRAC as public health focussed

• PRAC’s work - use of the new public health protection tools

• Looking ahead – what is still to come

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Pharmacovigilance legislative

aims

1. Clarity on roles and responsibilities

2. Proactive & proportionate safety monitoring

3. Robust and timely decision-making and consistent

action on safety issues

4. Greater inclusiveness for patients, healthcare

professionals

5. High levels of transparency

6. Best use of resources – avoid duplication

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Mandate of PRAC

All aspects of the risk management of the use of medicinal products including the detection,

assessment, minimisation and communication relating to the risk of adverse reactions, having due regard to

the therapeutic effect of the medicinal product, the design and evaluation of post-authorisation safety

studies and pharmacovigilance audit

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Membership of PRAC

Appointed by European

Commission:

Appointed by each

Member State:

1 member + alternate

28 + EEA countries non

voting members

6 members - relevant expertise including clinical pharmacology

and pharmacoepidemiology 1 member/alternate representing

patient organisations 1 member/alternate representing

healthcare professionals

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HCP and patient representatives

6

PRAC’s public health pillars

Proactive safety

monitoring & planning

Transparency

and

communication

Prompt

benefit risk

action

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PRAC - Tasks

• RMPs (initial and updates) for all centralised products;

• Signals – identification, prioritisation and evaluation;

• Periodic Safety Updates reports – single assessment;

• Risk minimisation measures and communications;

• Protocols for and results from non-interventional PASS;

• Safety referrals – recommendation to CHMP/CMDh;

- CHMP for referrals involving one CAP, EC final opinion

- CMDh for referrals for NAPs, EC opinion if no consensus

• Other safety related matters at CHMP or member state

request

• EURD and Additional monitoring lists

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RMP Advice/Assessments

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Proactive & planned

pharmacovigilance

Major PRAC focus on

signal detection – SMART

(Signal Management

Review Team):

- Tools and processes

- Methodological guidance

- Signal detection methods

Implementing Regulation 520/2012 “the Pharmacovigilance Risk Assessment

Committee shall regularly review the methodology(ies) used and publish

recommendations, as appropriate” [Art 20(3)]

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Signal Management Process

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Signal detection

Validation Confirmation Analysis,

prioritization Assessment

Recommendation for action

MAH

MSs

Agency

MSs Agency

PRAC

Signals – summary

Sept 2012 - Dec 2013

• 1 69 for CAPs, 43 for NAPs, 9 for both

• 2 6 referrals ongoing, 2 concluded: restriction of use (codeine) and suspension of MA (HES)

Data source

58 EudraVigilance

35 national review

11 literature

7 FDA/PMDA

5 historical (PhVWP)

6 studies

Outcome

57 labelling changes

17 no regulatory action

8 referral evaluation2

2 update RMP

37 ongoing assessment

Number of signals

1211

12

Monthly review by

PRAC of proposals

for additions to the

list

Communications

campaign starting

1 October 2012

Additional monitoring list

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PASS Protocols & Results

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Example of PASS

The applicant should conduct

a 5-year long-term

observational study with

ivacaftor in patients with cystic

fibrosis, including also

microbiological and clinical

endpoints (e.g. exacerbations),

according to a protocol agreed

with the CHMP

http://clinicaltrials.gov/ct2/show/NCT01117012?term=ivacaftor&rank=22

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Prompt benefit risk

recommendations

• Binding outcomes

from referrals

• Rigorous adherence

to legal timeframes

• PSURs as benefit

risk decision-making

tool

16

PRAC safety referrals

17

18

Urgent Union Procedure 107i

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Example 107i procedure –

Numeta 13%

• Numeta 13% parenteral nutrition

for preterm babies

• Signal of 14 reports of

hypermagnesaemia – July 2013

• Voluntary recall of Numeta 13%

• PRAC concludes advice

September 2013 to suspend

Numeta 13%, introduce risk

management for Numeta 16%

•

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Article 31 procedures

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Article 31 procedures

22

23

“EMA has started a review of

the risks of combining certain

medicines to block separate

stages of the renin-

angiotensin system (RAS) in

the treatment of hypertension

and congestive heart failure”

• 24 substances

• 37 CAPs

• > 16,000 NAPs

• 9 Rapporteurs

• Number of companies

involved unknown

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Stakeholder involvement

25

PSURs Outcomes

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Example –Strontium ranelate

Periodic safety update

report identified

increased risk of cardiac

disorders including MI

PRAC advised variation

to restrict MA on safety

grounds

CHMP started referral

under Art 31

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Transparency

28

Agenda is published on Day 1 of PRAC by mid-day

Meeting highlights are published on Friday of PRAC week

Safety referrals are published on Friday of PRAC week

Signal recommendations are published at the end of the month

Minutes are published on the following month after adoption

Highlights from

2-5 September

PRAC meeting,

published 6th

September

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Current PRAC priorities

• Increasing stakeholder

involvement

• Strengthening the science base

for benefit risk decision-making

• Optimising use of regulatory

tools for public health

• Measuring the public health

impact of activities

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Public Hearings

LEGAL BASIS

DEFINITION

OPENESS AND

TRANSPARENCY ORGANISATION

OBJECTIVES WHEN TO HOLD?

• Urgency matter permits

• Extent and seriousness

safety concerns

• Art. 107 and Art. 31

• All info public

• Part of overall assessment

• Declaration of Interests

• Recorded / video streamed

• Language challenge

• Website

• Specific questions

• Priority representatives

of groups / organisations

• Time allocation

• Public invited

• Stakeholders views and

concerns

• Specific questions

• Increased transparency

• Empower EU citizens

• Add value and increase

understanding

• Level of risk acceptance

• Define balance B/R

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Strengthening the science

base

33

Further legislation…

34

Optimising use of new tools

Referrals –scope,

criteria for triggering

Signal roles and

responsibilities,

methodologies

“EC Joint Action”

35

Joint Action - SCOPE

Strengthening Collaborations to Operate Pharmacovigilance in Europe

Facilitating collaboration among the Member States for the effective operation of the pharmacovigilance system in the EU

36

Public health outcomes

Demonstrably strengthening protection of public health–

what this is all about

37

Summary

• Establishment of PRAC is central to

implementation of EU Pharmacovigilance

legislation

• PRAC’s key focus - delivering the public health

objectives

• Experience demonstrates capability for robust

scientific decision making to rigorous timescales

• Major strides forward in transparency and

stakeholder involvement

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